We have undertaken a study of the mechanisms controlling the hepatic disposition of foreign compounds, especially chemical carcinogens and drugs. Emphasis is placed on the role of metabolism in this process. The interrelationships and interdependence of metabolism, binding and biliary excretion of the compounds are under investigation. Substances that will be examined include: (1) Aromatic hydrocarbon carcinogens. (2) Compounds that are excreted in the bile metabolically unchanged. (3) Compounds that are excreted in the bile after biotransformation. (4) Compounds that are metabolized in the liver but are excreted entirely in the urine. Included in this project are studies on certain hypolipidemic agents that induce choleresis and exert profound effects on the uptake, binding and biliary excretion of foreign compounds as well as physiological substances, e.g. bile salts and bilirubin. These effects will be used to shed light on hepatic uptake and biliary excretion mechanisms.